Za Pharmacy
Drugs, Supplies and Delivery
Imipramine
Imipramine is a tricyclic antidepressant (TCA) primarily used to treat major depressive disorder (MDD) and nocturnal enuresis (bedwetting) in children. Known for its dual inhibition of serotonin and norepinephrine reuptake, imipramine is effective but requires careful management due to its anticholinergic and cardiovascular side effects. This article synthesizes information from the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology to provide a detailed overview of imipramine, including its mechanism, uses, dosing, side effects, precautions, interactions, and availability.
Imipramine inhibits the reuptake of serotonin (5-HT) and norepinephrine (NE) at presynaptic neurons, enhancing their availability in the synaptic cleft. This improves mood regulation and arousal. Additionally, it blocks:
- Muscarinic Acetylcholine Receptors: Causes anticholinergic effects (e.g., dry mouth, constipation).
- Histamine H1 Receptors: Leads to sedation.
- Alpha-1 Adrenergic Receptors: Contributes to orthostatic hypotension (Lippincott Textbook of Pharmacology).
- Major Depressive Disorder (MDD):
- Effective for severe depression, though less commonly used due to side effects compared to newer antidepressants (BNF).
- Nocturnal Enuresis in Children (≥6 years):
- Reduces bedwetting by altering sleep patterns and bladder muscle tone (Lange Basic & Clinical Pharmacology).
- Off-Label Uses:
- Panic disorder, chronic neuropathic pain, and adjunct therapy for migraine prophylaxis (Lippincott).
- Adults (Depression):
- Initial Dose: 25–75 mg/day in divided doses or as a single nighttime dose.
- Maintenance Dose: 75–150 mg/day; maximum 200 mg/day (BNF).
- Children (Enuresis):
- 6–12 years: 25 mg 1 hour before bedtime, increased to 50 mg if needed.
- ≥12 years: 50–75 mg at bedtime (Lippincott).
Administration:
- Take at bedtime to minimize daytime sedation.
- Avoid abrupt discontinuation; taper gradually over 4 weeks to prevent withdrawal symptoms (Lange Basic & Clinical Pharmacology).
- Common: Dry mouth, constipation, blurred vision, sedation, weight gain, and orthostatic hypotension (BNF).
- Serious:
- Cardiac Arrhythmias: Due to QT prolongation, particularly in overdose.
- Seizures: Increased risk in predisposed individuals.
- Hyponatremia: Especially in elderly patients.
- Suicidal Ideation: Higher risk in adolescents and young adults (Lippincott).
- Contraindications:
- Recent myocardial infarction, arrhythmias, or severe liver/kidney impairment.
- Concurrent use of MAO inhibitors (BNF).
- Monitoring:
- ECG in patients with cardiac risk factors.
- Serum sodium levels in elderly patients.
- Pregnancy/Lactation:
- BNF Category C: Use only if benefits outweigh risks; potential neonatal withdrawal.
- Excreted in breast milk—use with caution (Lange Basic & Clinical Pharmacology).
- MAO Inhibitors: Risk of serotonin syndrome; allow a 14-day washout period (BNF).
- CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): Increase imipramine levels; monitor for toxicity.
- Anticholinergic Drugs (e.g., antihistamines, antipsychotics): Enhanced dry mouth, constipation, and urinary retention.
- QT-Prolonging Drugs (e.g., amiodarone, citalopram): Increased arrhythmia risk (Lippincott).
Imipramine is the generic name. Brand names include Tofranil®. Generic formulations are widely available as:
- Tablets: 10 mg, 25 mg, 50 mg.
- Oral Solution: 25 mg/5 mL (BNF).
